Nakanishi T, Yamauchi A, Nakahama H, Yamamura Y, Yamada Y, Orita Y, Fujiwara Y, Uyeda N, Takamitsu Y, Sugita M
Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Am J Physiol. 1994 Jul;267(1 Pt 2):F146-52. doi: 10.1152/ajprenal.1994.267.1.F146.
For the purpose of clarifying the role of vasopressin V1 and V2 receptors in osmolyte accumulation, we determined the effects on the inner medullary osmolyte content of the administration of orally active vasopressin V1 and/or V2 receptor antagonists OPC-21268 (i.e., 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)- 3,4-dihydro-2(1H)-quinolinone) and OPC-31260 (i.e., 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tet rah ydro-1H- benzazepine] under a condition of maximal urine concentration achieved by water deprivation for 4 days. Taurine content increased significantly with the use of the V2 antagonist, irrespective of the use of the V1 antagonist. Inner medullary betaine content decreased with the administration of the V1 antagonist, irrespective of the administration of V2 antagonist. The administration of either the V1 or V2 antagonist alone did not affect sorbitol content, aldose reductase activity, or aldose reductase mRNA abundance in renal inner medulla. However, the combined administration of the V1 and V2 antagonists decreased all of these significantly. Myo-inositol content was not affected by the administration of the V1 or V2 antagonists. Glycerophosphorylcholine content was decreased with the use of the V2 antagonist, irrespective of the use of the V1 antagonist, and this effect paralleled urine osmolality. In conclusion, the individual organic osmolytes responded differently to the antagonists of vasopressin V1 and/or V2 receptors. The mechanisms linked to vasopressin V1 and/or V2 receptors appeared to modulate the accumulation of some organic osmolytes in the inner medulla. Aldose reductase mRNA abundance and sorbitol accumulation in the inner medulla appeared to be mediated through either V1 or V2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
为了阐明血管加压素V1和V2受体在渗透溶质蓄积中的作用，我们测定了口服活性血管加压素V1和/或V2受体拮抗剂OPC - 21268（即1 - (1 - [4 - (3 - 乙酰氨基丙氧基)苯甲酰基]-4 - 哌啶基)-3,4 - 二氢 - 2(1H)-喹啉酮）和OPC - 31260（即5 - 二甲氨基 - 1 - [4 - (2 - 甲基苯甲酰胺基)苯甲酰基]-2,3,4,5 - 四氢 - 1H - 苯并氮杂䓬）对肾内髓渗透溶质含量的影响，实验条件为通过4天禁水达到最大尿浓缩状态。无论是否使用V1拮抗剂，使用V2拮抗剂后牛磺酸含量均显著增加。无论是否使用V2拮抗剂，给予V1拮抗剂后肾内髓部甜菜碱含量均降低。单独给予V1或V2拮抗剂均不影响肾内髓中山梨醇含量、醛糖还原酶活性或醛糖还原酶mRNA丰度。然而，联合给予V1和V2拮抗剂可使所有这些指标显著降低。肌醇含量不受V1或V2拮抗剂给药的影响。无论是否使用V1拮抗剂，使用V2拮抗剂后甘油磷酸胆碱含量均降低，且这种影响与尿渗透压平行。总之，各个有机渗透溶质对血管加压素V1和/或V2受体拮抗剂的反应不同。与血管加压素V1和/或V2受体相关的机制似乎调节了肾内髓中一些有机渗透溶质的蓄积。肾内髓中醛糖还原酶mRNA丰度和山梨醇蓄积似乎是通过V1或V2受体介导的。（摘要截短至250字）
